Aging is associated with well documented alterations in immune responses. For CD4+ T cells from aged mice, activation leads to depressed proliferative responses by comparison to T cells from young mice and production of elevated levels of a variety of cytokines including IL-4, IFN-gamma, IL-10 and TNF. IL-2 production is frequently lower than normal. The extent to which these changes reflect the accumulation of memory cells with advancing age is not yet resolved as some studies report deficits in the responses of both memory and naive T cells from older animals. In this proposal, TCR transgenic mice will be used to examine the requirement for antigen induced differentiation in the development of age associated alterations in CD4+ T cell phenotype and function. Experiments are also proposed to determine whether the aging microenvironment plays a role in maintaining age-related changes in CD4+ cell function in this system. Finally, we will evaluate the relative antigen presenting cell function of purified populations of antigen presenting cells from aged mice including splenic dendritic cells, macrophages and B cells. These experiments will provide an important foundation for future studies to further define the mechanisms involved in the poor immune responses of older individuals.